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Proteomic and genomic signatures of repeat instability in cancer and adjacent normal tissues.

Abstract：

:Repetitive sequences are hotspots of evolution at multiple levels. However, due to difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content, beyond microsatellites, in proteomes and genomes directly from proteomic and genomic raw data. This method was applied to a wide range of tumors and normal tissues. We identify high similarity between repeat instability patterns in tumors and their patient-matched adjacent normal tissues. Nonetheless, tumor-specific signatures both in protein expression and in the genome strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We observe an inverse relationship between repeat instability and point mutation load within and across patients independent of other somatic aberrations. Thus, repeat instability is a distinct, transient, and compensatory adaptive mechanism in tumor evolution and a potential signal for early detection.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Persi E,Prandi D,Wolf YI,Pozniak Y,Barnabas GD,Levanon K,Barshack I,Barbieri C,Gasperini P,Beltran H,Faltas BM,Rubin MA,Geiger T,Koonin EV,Demichelis F,Horn D

doi

10.1073/pnas.1908790116

subject

Has Abstract

pub_date

2019-08-20 00:00:00

pages

16987-16996

issue

34

eissn

0027-8424

issn

1091-6490

pii

1908790116

journal_volume

116

pub_type

杂志文章

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